DOPAMINE HCL

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if the solution is darker than slightly yellow or discolored in any other way.
-A sulfur dioxide odor may occur upon removal of the Viaflex Plus containers from the overwrap; this does not pose risk to the clinician or patient using the product.
-Correct hypovolemia before dopamine administration.
Intravenous Administration
Dilution
-Dilute dopamine concentrate for injection with a compatible IV solution (i.e., 5% Dextrose Injection, 0.9% Sodium Chloride Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and Lactated Ringer's Injection, Lactated Ringer's Injection) to yield a concentration of 200 to 1,600 mcg/mL.
-Do not add dopamine to Sodium Bicarbonate Injection or other alkaline intravenous solutions since the drug is inactivated in alkaline solution.
-Institute for Safe Medication Practices (ISMP)/Vermont Oxford Network (VON) Recommended Standard Concentration for Neonatal Infusions: 1,600 mcg/mL.
-Concentrations up to 6,400 mcg/mL have been reported.
-Storage: Dilutions are stable for 24 hours.

Continuous IV Infusion
-Administer using a controlled infusion device.
-Infuse into a large vein whenever possible to prevent extravasation into tissue adjacent to the infusion site. Large veins of the antecubital fossa are preferred over veins in the dorsum of the hand or ankle. Use less suitable infusion sites only if the patient's condition requires immediate attention; switch to more suitable sites as rapidly as possible. Continuously monitor the infusion site for free flow. Do not administer via umbilical artery catheter (UAC).
-Avoid inadvertent bolus administration or inadvertent interruption of the infusion, particularly during line changes, when flushing the line, or during syringe/bag changes.
-Do not administer solutions containing dextrose through the same administration set as blood, as it may result in pseudoagglutination or hemolysis.
-Monitor urine flow, cardiac output, and blood pressure; titrate to patient response.
-Consider dosage reduction or temporary suspension of the infusion for decreased urine flow, increased tachycardia, or the development of new arrhythmias.
-Upon discontinuation, gradually decrease the dose while expanding blood volume with intravenous fluids to avoid hypotension.

Extravasation Management
NOTE: Extravasation management instructions are provided in the product labeling; instructions are not specific to pediatric patients and may require adjustments for some patients (e.g., smaller volumes for neonates and infants).
-If extravasation occurs, infiltrate the site with 10 to 15 mL of 0.9% Sodium Chloride Injection containing 5 to 10 mg of phentolamine.
-Use a syringe with a fine hypodermic needle and liberally infiltrate throughout the ischemic area.
-Administer phentolamine solution as quickly as possible after extravasation to minimize tissue damage; sympathetic blockade with phentolamine causes immediate and noticeable local hyperemic changes if the area is infiltrated within 12 hours of extravasation.

Other Injectable Administration
Intraosseous Administration
NOTE: Dopamine is not FDA-approved for intraosseous administration.
-During cardiopulmonary resuscitation, the same dosage may be given via the intraosseous route if IV access is unsuccessful or not feasible.

Ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation), atrial fibrillation, ectopic beats (e.g., premature ventricular contractions (PVCs), premature atrial contractions (PACs)), sinus tachycardia, angina, palpitations, cardiac conduction abnormalities, widened QRS complex, and bradycardia have been observed with dopamine use. Monitor cardiac output and blood pressure during dopamine infusion. If increasing tachycardia or new dysrhythmias develop, consider reducing the dose or temporarily discontinuing dopamine. Reduce the dopamine infusion rate if an increased number of ectopic beats is observed. Reduce the dopamine infusion rate if an increased number of ectopic beats is observed.

Extravasation of dopamine may cause tissue necrosis, sloughing, and gangrene. Infuse dopamine into a large vein whenever possible. Large veins of the antecubital fossa are preferred over veins in the dorsum of the hand or ankle. Use less suitable infusion sites only if the patient's condition requires immediate attention; switch to more suitable sites as rapidly as possible. Continuously monitor the infusion site for free flow. To prevent sloughing and necrosis in ischemic areas, infiltrate the area as soon as possible with 10 to 15 mL of 0.9% Sodium Chloride Injection containing 5 to 10 mg of phentolamine; administer the solution liberally throughout the ischemic area using a fine hypodermic needle. Sympathetic blockade with phentolamine causes immediate and noticeable local hyperemic changes if the area is infiltrated within 12 hours of extravasation. Gangrene of the extremities has occurred when high doses of dopamine were administered for prolonged periods or in patients with occlusive vascular disease receiving low doses of dopamine. In neonates, vasospastic events have been reported when dopamine was infused through an umbilical vessel.

Peripheral vasoconstriction has been observed with dopamine use and can result from the alpha-stimulation associated with high-dose dopamine. Hypertension has also been observed with dopamine use. Closely monitor blood pressure and peripheral perfusion. Dopamine infusion rates of more than 20 mcg/kg/minute increase heart rate and right atrial pressure and may result in excessive splanchnic vasoconstriction.

Hypotension has been observed with dopamine use and may occur at infusion rates at the lower end of the dosage range due to vasodilation that occurs with low doses. If hypotension occurs at lower infusion rates, rapidly titrate the dose until adequate blood pressure is obtained. If hypotension persists, discontinue dopamine and initiate a more potent vasoconstrictor (e.g., norepinephrine). Abrupt discontinuation of dopamine may also result in significant hypotension. When discontinuing the dopamine infusion, it may be necessary to gradually decrease the dopamine dose while expanding blood volume.

Dyspnea, nausea, vomiting, headache, anxiety, and piloerection (gooseflesh) have been observed with dopamine use.

Azotemia has been observed with dopamine use. Monitor urine output closely; if a reduction in urine output is noted, consider reducing the dose or temporarily discontinuing dopamine.

Solutions containing dextrose (e.g., premixed bags) may be contraindicated in patients with corn hypersensitivity. Certain formulations of dopamine contain sodium bisulfite. Sodium bisulfite is a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe episodes in certain susceptible people, such as patients with sulfite hypersensitivity or asthma.

Dopamine is contraindicated in patients with pheochromocytoma or uncorrected tachyarrhythmias including ventricular fibrillation and ventricular tachycardia. Reduce the dopamine dose if an increased number of ectopic beats is observed.

Correct hypovolemia before dopamine administration. Monitoring of central venous pressure (CVP) or left ventricular filling pressure may be helpful in detecting and treating hypovolemia.

If a disproportionate rise in diastolic pressure occurs (i.e., decreased pulse pressure), decrease the dopamine infusion rate and monitor the patient for further evidence of predominant vasoconstrictor activity, unless such an effect is desired. Monitor patients with a history of occlusive vascular disease (e.g., atherosclerosis, arterial embolism, Raynaud's phenomenon, diabetic endarteritis, thromboangiitis obliterans (Buerger's disease)) for changes in the color or temperature of the skin in the extremities. If such changes occur, weigh the benefits of continued dopamine use against the risk of possible necrosis. This condition may be reversed by either decreasing the rate or discontinuing the infusion.

Infuse dopamine into a large vein whenever possible to prevent extravasation into tissue adjacent to the infusion site. Large veins of the antecubital fossa are preferred over veins in the dorsum of the hand or ankle. Use less suitable infusion sites only if the patient's condition requires immediate attention; switch to more suitable sites as rapidly as possible. Continuously monitor the infusion site for free flow. If extravasation occurs, infiltrate the affected area with phentolamine as soon as possible; administer the solution liberally throughout the ischemic area using a fine hypodermic needle. Sympathetic blockade with phentolamine causes immediate and noticeable local hyperemic changes if the area is infiltrated within 12 hours of extravasation.

Abrupt discontinuation of dopamine may result in significant hypotension. When discontinuing the dopamine infusion, it may be necessary to gradually decrease the dopamine dose while expanding blood volume.

Identify and correct hypoxemia, hypercapnia, respiratory acidosis, and metabolic acidosis before and concurrently with the administration of dopamine. These conditions may reduce the effectiveness of and/or increase the incidence of adverse effects of dopamine.

Use caution if umbilical vessel administration of dopamine becomes necessary in the neonate. Vasospastic events have been reported when dopamine was infused through umbilical vessels.

Description: Dopamine is an intravenous dopaminergic and adrenergic agonist with dose-dependent clinical effects. Dopamine exerts inotropic, chronotropic, and vasopressor effects, making it useful for the treatment of decreased cardiac output and hypotension associated with septic shock, cardiogenic shock, trauma, surgery, and heart failure. Dopamine is not considered a first-line vasopressor in pediatric patients with fluid-refractory septic shock but may be used if epinephrine or norepinephrine are not readily available. Compared to epinephrine, dopamine is associated with a higher risk of mortality and fewer organ failure-free days in this population. During cardiopulmonary resuscitation, dopamine may be used to treat hypotension, particularly when it is associated with symptomatic bradycardia or after the return of spontaneous circulation (ROSC). The routine use of low-dose dopamine for the treatment or prevention of acute renal failure is no longer recommended. While low-dose dopamine infusions dilate renal arterioles and increase renal blood flow and glomerular filtration rate, clinical studies in adults have not shown dopamine to be effective in the treatment of oliguric acute renal failure. In addition, evidence from clinical trials in adults shows that low-dose dopamine does not prevent acute renal failure in critically ill patients with early renal dysfunction. Dopamine is not FDA-approved in pediatric patients but is used clinically in patients as young as neonates.

General dosing information
-The clinical effects of dopamine are dose-dependent. At low doses (less than 5 mcg/kg/minute), dopamine increases renal blood flow and urine output. At intermediate doses (5 to 10 mcg/kg/minute), dopamine continues to increase renal blood flow, but also increases cardiac contractility and chronotropy with a mild increase in systemic vascular resistance. At high doses, dopamine maintains this beta-activity while preferentially targeting alpha-receptors, resulting in vasoconstriction. Clinical effects in neonatal patients at varying doses are not always consistent or clearly defined; variations in developmental pharmacology necessitate careful dosage adjustments and monitoring in these patients.
-Correct hypovolemia before dopamine administration.
-Monitor urine flow, cardiac output, and blood pressure; titrate to the desired hemodynamic and/or renal response. Consider dosage reduction or temporary suspension of the infusion for decreased urine flow, increased tachycardia, or the development of new arrhythmias.
-Upon discontinuation, gradually decrease the dose while expanding blood volume with intravenous fluids to avoid marked low blood pressure.

For hemodynamic support during septic shock*, cardiogenic shock*, trauma*, surgery*, and heart failure*, and for the treatment of hypotension* that may occur after return of spontaneous circulation during cardiopulmonary resuscitation* after cardiac arrest*:
Continuous Intravenous or Intraosseous* Infusion dosage:
Neonates: 1 to 5 mcg/kg/minute continuous IV or IO infusion, initially. Titrate by 2.5 to 5 mcg/kg/minute until desired hemodynamic response is attained. Usual Max: 15 to 20 mcg/kg/minute. Infusion rates more than 20 mcg/kg/minute may result in vasoconstriction.
Infants, Children, and Adolescents: 1 to 5 mcg/kg/minute continuous IV or IO infusion, initially. Titrate by 2.5 to 5 mcg/kg/minute until desired hemodynamic response is attained. Usual Max: 15 to 20 mcg/kg/minute. Infusion rates more than 20 mcg/kg/minute may result in vasoconstriction.

Maximum Dosage Limits:
-Neonates
20 mcg/kg/minute continuous IV infusion.
-Infants
20 mcg/kg/minute continuous IV infusion.
-Children
20 mcg/kg/minute continuous IV infusion.
-Adolescents
20 mcg/kg/minute continuous IV infusion.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Dopamine is the metabolic precursor to norepinephrine in the catecholamine synthetic pathway; it has sites of action in both the central and peripheral nervous systems. Dopamine increases blood pressure and mean arterial pressure (MAP) by increasing myocardial contractility and peripheral vasoconstriction. The clinical effects of exogenous dopamine vary depending on the rate of infusion. At low doses (less than 5 mcg/kg/minute), dopamine targets dopaminergic D1 receptors in the renal, mesenteric, coronary, and cerebral vasculature and D2 receptors in the vasculature and renal tissue, promoting vasodilation and increased blood flow to these tissues. At intermediate doses (5 to 10 mcg/kg/minute), dopamine continues to stimulate dopaminergic receptors but also activities beta1-receptors, which results in increased cardiac contractility and chronotropy with a mild increase in systemic vascular resistance. At high doses, dopamine maintains beta activity while preferentially targeting alpha-receptors, resulting in potent vasoconstriction.

Pharmacokinetics: Dopamine is administered intravenously. It is widely distributed throughout the body but does not cross the blood-brain barrier to a significant extent. Dopamine is metabolized in the liver, kidneys, and plasma to inactive compounds by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). About 25% of the dose is taken up into adrenergic nerve terminals where it is hydroxylated to form norepinephrine. Excretion occurs in the urine, mainly as metabolites and conjugates. Plasma half-life is about 2 minutes.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Intravenous Route
Onset of action occurs within 5 minutes and persists for less than 10 minutes.


-Special Populations
Pediatrics
Neonates
The plasma clearance of dopamine was dose-dependent in a study of 14 preterm and term neonates (gestational age 27 to 42 weeks), decreasing from 60 +/- 12 mL/kg/minute at the lowest infusion rate (1 to 2 mcg/kg/minute) to 48 +/- 6 mL/kg/minute at the highest infusion rate (4 to 8 mcg/kg/minute). Clearance did not vary with birth weight or gestational age. Although data were limited, study results suggest increases in cardiac output occur at thresholds at or below those needed for increases in blood pressure in this population.

Infants, Children, and Adolescents
Patients younger than 2 years had a significantly faster clearance than those older than 2 years (82.3 +/- 27.7 mL/kg/minute vs. 45.9 +/- 17 mL/kg/minute) in a study of pediatric patients (n = 27, age 2 days to 18 years).

Renal Impairment
Mean plasma clearance of dopamine was slower in critically ill pediatric patients (n = 6, age 2 days to 180 months) with renal dysfunction (SCr more than 1.2 mg/dL or BUN more than 25 mg/dL) compared to patients without renal dysfunction (25.8 mL/kg/minute vs. 76.8 mL/kg/minute). The 2 patients with the slowest dopamine clearance (10 and 10.5 mL/kg/minute) also had concomitant liver dysfunction.